The Cerebellum in Niemann-Pick C1 Disease: Mouse Versus Man.
Cerebellum
; 22(1): 102-119, 2023 Feb.
Article
en En
| MEDLINE
| ID: mdl-35040097
ABSTRACT
Selective neuronal vulnerability is common to most degenerative disorders, including Niemann-Pick C (NPC), a rare genetic disease with altered intracellular trafficking of cholesterol. Purkinje cell dysfunction and loss are responsible for cerebellar ataxia, which is among the prevailing neurological signs of the NPC disease. In this review, we focus on some questions that are still unresolved. First, we frame the cerebellar vulnerability in the context of the extended postnatal time length by which the development of this structure is completed in mammals. In line with this thought, the much later development of cerebellar symptoms in humans is due to the later development and/or maturation of the cerebellum. Hence, the occurrence of developmental events under a protracted condition of defective intracellular cholesterol mobilization hits the functional maturation of the various cell types generating the ground of increased vulnerability. This is particularly consistent with the high cholesterol demand required for cell proliferation, migration, differentiation, and synapse formation/remodeling. Other major questions we address are why the progression of Purkinje cells loss is always from the anterior to the posterior lobes and why cerebellar defects persist in the mouse model even when genetic manipulations can lead to nearly normal survival.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Enfermedad de Niemann-Pick Tipo C
Límite:
Animals
/
Humans
/
Male
Idioma:
En
Revista:
Cerebellum
Asunto de la revista:
CEREBRO
Año:
2023
Tipo del documento:
Article
País de afiliación:
Italia